In this competitive renewal of our Institutional Center Core Grant to support neuroscience research, we propose to maintain and expand the operation of three existing Core facilities at the Johns Hopkins University School of Medicine (JHU SOM) that were established during the previous funding period of this Center Grant: a Multiphoton Imaging Core, a Monoclonal Antibody Core, and an Embryonic Stem Cell Engineering Core. These facilities currently provide necessary resources and perform required services that impractical for individual laboratories to provide on their own. Use of these Core facilities will continue to greatly benefit NINDS-funded research programs of the eleven Primary Center Investigators, and also other NINDS-funded investigators at JHU SOM, by providing access to unique equipment, training in new methodologies, and development of new reagents. The experimental opportunities and technical services offered by these three Cores complement, but do not duplicate, other Core facilities available to NINDSfunded investigators at JHU SOM. Seven of the eleven Primary Center Investigators are members of the Department of Neuroscience, four are members of the Department of Neurology,a nd one is in the Department of Pathology. The research programs of the Primary Center Investigators address unresolved issues in the areas of neural and glial development, synaptic structure and function, sensory transduction, and activity-dependent regulation of gene expression. The Specific Aims of Primary Center Investigators'NINDS-funded research programs address critical clinical issues, including the developmental origins of neurological disorders, the promotion of neuronal regeneration following injury or degeneration, the underlying basis of neuropathic pain, and the origin of neurodegenerative disorders (Alzheimer's Dementia and Amyotrophic Lateral Sclerosis). The Primary Center Investigators constitute a highly interactive group with a history of seamless collaborative research efforts. The goal of this Center is to augment existing research programs by providing these investigators, and other NINDS-funded investigators at JHU SOM, with Core facilities that are not available elsewhere at this institution.